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Q02956

- KPCZ_MOUSE

UniProt

Q02956 - KPCZ_MOUSE

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Protein

Protein kinase C zeta type

Gene

Prkcz

Organism
Mus musculus (Mouse)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli

Functioni

Calcium- and diacylglycerol-independent serine/threonine-protein kinase that functions in phosphatidylinositol 3-kinase (PI3K) pathway and mitogen-activated protein (MAP) kinase cascade, and is involved in NF-kappa-B activation, mitogenic signaling, cell proliferation, cell polarity, inflammatory response and maintenance of long-term potentiation (LTP). Upon lipopolysaccharide (LPS) treatment in macrophages, or following mitogenic stimuli, functions downstream of PI3K to activate MAP2K1/MEK1-MAPK1/ERK2 signaling cascade independently of RAF1 activation. Required for insulin-dependent activation of AKT3, but may function as an adapter rather than a direct activator. Upon insulin treatment may act as a downstream effector of PI3K and contribute to the activation of translocation of the glucose transporter SLC2A4/GLUT4 and subsequent glucose transport in adipocytes. In EGF-induced cells, binds and activates MAP2K5/MEK5-MAPK7/ERK5 independently of its kinase activity and can activate JUN promoter through MEF2C. Through binding with SQSTM1/p62, functions in interleukin-1 signaling and activation of NF-kappa-B with the specific adapters RIPK1 and TRAF6. Participates in TNF-dependent transactivation of NF-kappa-B by phosphorylating and activating IKBKB kinase, which in turn leads to the degradation of NF-kappa-B inhibitors. In migrating astrocytes, forms a cytoplasmic complex with PARD6A and is recruited by CDC42 to function in the establishment of cell polarity along with the microtubule motor and dynein. In association with FEZ1, stimulates neuronal differentiation in PC12 cells. In the inflammatory response, is required for the T-helper 2 (Th2) differentiation process, including interleukin production, efficient activation of JAK1 and the subsequent phosphorylation and nuclear translocation of STAT6. May be involved in development of allergic airway inflammation (asthma), a process dependent on Th2 immune response. In the NF-kappa-B-mediated inflammatory response, can relieve SETD6-dependent repression of NF-kappa-B target genes by phosphorylating the RELA subunit at 'Ser-311'. Necessary and sufficient for LTP maintenance in hippocampal CA1 pyramidal cells. In vein endothelial cells treated with the oxidant peroxynitrite, phosphorylates STK11 leading to nuclear export of STK11, subsequent inhibition of PI3K/Akt signaling, and increased apoptosis.2 Publications

Catalytic activityi

ATP + a protein = ADP + a phosphoprotein.

Enzyme regulationi

Atypical PKCs (PRKCI and PRKCZ) exhibit an elevated basal enzymatic activity (that may be due to the interaction with SMG1 or SQSTM1) and are not regulated by diacylglycerol, phosphatidylserine, phorbol esters or calcium ions. Two specific sites, Thr-410 (activation loop of the kinase domain) and Thr-560 (turn motif), need to be phosphorylated for its full activation. Phosphatidylinositol 3,4,5-trisphosphate might be a physiological activator By similarity.By similarity

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Binding sitei281 – 2811ATPPROSITE-ProRule annotation
Active sitei376 – 3761Proton acceptorPROSITE-ProRule annotation

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Zinc fingeri130 – 18051Phorbol-ester/DAG-typePROSITE-ProRule annotationAdd
BLAST
Nucleotide bindingi258 – 2669ATPPROSITE-ProRule annotation

GO - Molecular functioni

  1. ATP binding Source: UniProtKB-KW
  2. potassium channel regulator activity Source: Ensembl
  3. protein kinase activity Source: MGI
  4. protein kinase C activity Source: UniProtKB-EC
  5. protein serine/threonine kinase activity Source: UniProtKB
  6. zinc ion binding Source: InterPro

GO - Biological processi

  1. actin cytoskeleton reorganization Source: Ensembl
  2. activation of phospholipase D activity Source: Ensembl
  3. activation of protein kinase B activity Source: Ensembl
  4. cell migration Source: Ensembl
  5. establishment of cell polarity Source: UniProtKB
  6. inflammatory response Source: UniProtKB-KW
  7. insulin receptor signaling pathway Source: Ensembl
  8. long-term memory Source: Ensembl
  9. long-term synaptic potentiation Source: UniProtKB
  10. membrane hyperpolarization Source: Ensembl
  11. microtubule cytoskeleton organization Source: MGI
  12. negative regulation of apoptotic process Source: Ensembl
  13. negative regulation of hydrolase activity Source: Ensembl
  14. negative regulation of insulin receptor signaling pathway Source: Ensembl
  15. negative regulation of peptidyl-tyrosine phosphorylation Source: Ensembl
  16. negative regulation of protein complex assembly Source: Ensembl
  17. neuron projection extension Source: MGI
  18. peptidyl-serine phosphorylation Source: Ensembl
  19. positive regulation of cell-matrix adhesion Source: Ensembl
  20. positive regulation of cell proliferation Source: Ensembl
  21. positive regulation of ERK1 and ERK2 cascade Source: UniProtKB
  22. positive regulation of excitatory postsynaptic membrane potential Source: UniProtKB
  23. positive regulation of glucose import Source: Ensembl
  24. positive regulation of insulin receptor signaling pathway Source: UniProtKB
  25. positive regulation of interleukin-10 secretion Source: UniProtKB
  26. positive regulation of interleukin-13 secretion Source: UniProtKB
  27. positive regulation of interleukin-4 production Source: UniProtKB
  28. positive regulation of interleukin-5 secretion Source: UniProtKB
  29. positive regulation of NF-kappaB transcription factor activity Source: UniProtKB
  30. positive regulation of T-helper 2 cell cytokine production Source: UniProtKB
  31. positive regulation of T-helper 2 cell differentiation Source: UniProtKB
  32. protein heterooligomerization Source: Ensembl
  33. protein kinase C signaling Source: Ensembl
  34. protein localization to plasma membrane Source: MGI
  35. protein phosphorylation Source: MGI
  36. vesicle transport along microtubule Source: Ensembl
Complete GO annotation...

Keywords - Molecular functioni

Kinase, Serine/threonine-protein kinase, Transferase

Keywords - Biological processi

Inflammatory response

Keywords - Ligandi

ATP-binding, Metal-binding, Nucleotide-binding, Zinc

Enzyme and pathway databases

BRENDAi2.7.11.13. 3474.
ReactomeiREACT_196549. TGF-beta receptor signaling in EMT (epithelial to mesenchymal transition).
REACT_220092. GPVI-mediated activation cascade.

Names & Taxonomyi

Protein namesi
Recommended name:
Protein kinase C zeta type (EC:2.7.11.13)
Alternative name(s):
nPKC-zeta
Gene namesi
Name:Prkcz
Synonyms:Pkcz
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
ProteomesiUP000000589: Chromosome 4

Organism-specific databases

MGIiMGI:97602. Prkcz.

Subcellular locationi

Cytoplasm By similarity. Endosome By similarity. Cell junction By similarity
Note: In the retina, localizes in the terminals of the rod bipolar cells. Associated with endosomes. Presence of KRIT1, CDH5 and RAP1B is required for its localization to the cell junction By similarity.By similarity

GO - Cellular componenti

  1. apical cortex Source: MGI
  2. apical plasma membrane Source: MGI
  3. axon hillock Source: MGI
  4. cell-cell junction Source: UniProtKB
  5. cell cortex Source: MGI
  6. cell leading edge Source: Ensembl
  7. cytoplasm Source: MGI
  8. cytosol Source: Ensembl
  9. endosome Source: UniProtKB-KW
  10. extracellular vesicular exosome Source: Ensembl
  11. membrane raft Source: Ensembl
  12. microtubule organizing center Source: MGI
  13. myelin sheath abaxonal region Source: BHF-UCL
  14. nuclear envelope Source: MGI
  15. nuclear matrix Source: MGI
  16. nucleus Source: MGI
  17. perinuclear region of cytoplasm Source: Ensembl
  18. plasma membrane Source: MGI
  19. protein complex Source: MGI
  20. tight junction Source: MGI
Complete GO annotation...

Keywords - Cellular componenti

Cell junction, Cytoplasm, Endosome

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 592592Protein kinase C zeta typePRO_0000055702Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei410 – 4101Phosphothreonine; by PDPK1 and PI3KBy similarity
Modified residuei560 – 5601PhosphothreonineBy similarity

Post-translational modificationi

CDH5 is required for its phosphorylation at Thr-410. Phosphorylated by protein kinase PDPK1; phosphorylation is inhibited by the apoptotic C-terminal cleavage product of PKN2. Phosphorylation at Thr-410 by PI3K activates the kinase By similarity.By similarity

Keywords - PTMi

Phosphoprotein

Proteomic databases

MaxQBiQ02956.
PaxDbiQ02956.
PRIDEiQ02956.

PTM databases

PhosphoSiteiQ02956.

Expressioni

Gene expression databases

BgeeiQ02956.
CleanExiMM_PRKCZ.
ExpressionAtlasiQ02956. baseline and differential.
GenevestigatoriQ02956.

Interactioni

Subunit structurei

Interacts directly with SQSTM1. Forms a ternary complex with SQSTM1 and KCNAB2. Forms another ternary complex with SQSTM1 and GABRR3. Forms a complex with SQSTM1 and MAP2K5 By similarity. Interacts with PARD6A, PARD6B and PARD6G. Part of a complex with PARD3, PARD6A or PARD6B or PARD6G and CDC42 or RAC1. Interacts with ADAP1/CENTA1. Interacts (via the protein kinase domain) with WWC1. Forms a tripartite complex with WWC1 and DDR1, but predominantly in the absence of collagen. Interacts with PDPK1 (via N-terminal region) By similarity.By similarity

Protein-protein interaction databases

BioGridi202203. 10 interactions.
IntActiQ02956. 3 interactions.
MINTiMINT-98101.

Structurei

3D structure databases

ProteinModelPortaliQ02956.
SMRiQ02956. Positions 13-182, 184-584.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini15 – 9884OPRAdd
BLAST
Domaini252 – 518267Protein kinasePROSITE-ProRule annotationAdd
BLAST
Domaini519 – 59072AGC-kinase C-terminalAdd
BLAST

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni79 – 14567Interaction with SQSTM1By similarityAdd
BLAST

Domaini

The C1 domain does not bind the diacylglycerol (DAG).
The OPR domain mediates mutually exclusive interactions with SQSTM1 and PARD6B.By similarity

Sequence similaritiesi

Contains 1 AGC-kinase C-terminal domain.Curated
Contains 1 OPR domain.Curated
Contains 1 phorbol-ester/DAG-type zinc finger.PROSITE-ProRule annotation
Contains 1 protein kinase domain.PROSITE-ProRule annotation

Zinc finger

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Zinc fingeri130 – 18051Phorbol-ester/DAG-typePROSITE-ProRule annotationAdd
BLAST

Keywords - Domaini

Zinc-finger

Phylogenomic databases

eggNOGiCOG0515.
GeneTreeiENSGT00760000118891.
HOGENOMiHOG000233033.
HOVERGENiHBG108317.
InParanoidiQ02956.
KOiK06069.
OMAiRCHVLVP.
OrthoDBiEOG7HF1J3.
TreeFamiTF102004.

Family and domain databases

InterProiIPR000961. AGC-kinase_C.
IPR020454. DAG/PE-bd.
IPR011009. Kinase-like_dom.
IPR000270. OPR_PB1.
IPR002219. PE/DAG-bd.
IPR012233. PKC_zeta.
IPR017892. Pkinase_C.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR002290. Ser/Thr_dual-sp_kinase.
IPR008271. Ser/Thr_kinase_AS.
[Graphical view]
PANTHERiPTHR24357:SF60. PTHR24357:SF60. 1 hit.
PfamiPF00130. C1_1. 1 hit.
PF00564. PB1. 1 hit.
PF00069. Pkinase. 1 hit.
PF00433. Pkinase_C. 1 hit.
[Graphical view]
PIRSFiPIRSF000554. PKC_zeta. 1 hit.
PRINTSiPR00008. DAGPEDOMAIN.
SMARTiSM00109. C1. 1 hit.
SM00666. PB1. 1 hit.
SM00133. S_TK_X. 1 hit.
SM00220. S_TKc. 1 hit.
[Graphical view]
SUPFAMiSSF56112. SSF56112. 1 hit.
PROSITEiPS51285. AGC_KINASE_CTER. 1 hit.
PS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
PS00479. ZF_DAG_PE_1. 1 hit.
PS50081. ZF_DAG_PE_2. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Q02956-1 [UniParc]FASTAAdd to Basket

« Hide

        10         20         30         40         50
MPSRTDPKMD RSGGRVRLKA HYGGDILITS VDAMTTFKDL CEEVRDMCGL
60 70 80 90 100
HQQHPLTLKW VDSEGDPCTV SSQMELEEAF RLVCQGRDEV LIIHVFPSIP
110 120 130 140 150
EQPGMPCPGE DKSIYRRGAR RWRKLYRANG HLFQAKRFNR GAYCGQCSER
160 170 180 190 200
IWGLSRQGYR CINCKLLVHK RCHVLVPLTC RRHMDSVMPS QEPPVDDKND
210 220 230 240 250
GVDLPSEETD GIAYISSSRK HDNIKDDSED LKPVIDGVDG IKISQGLGLQ
260 270 280 290 300
DFDLIRVIGR GSYAKVLLVR LKKNDQIYAM KVVKKELVHD DEDIDWVQTE
310 320 330 340 350
KHVFEQASSN PFLVGLHSCF QTTSRLFLVI EYVNGGDLMF HMQRQRKLPE
360 370 380 390 400
EHARFYAAEI CIALNFLHER GIIYRDLKLD NVLLDADGHI KLTDYGMCKE
410 420 430 440 450
GLGPGDTTST FCGTPNYIAP EILRGEEYGF SVDWWALGVL MFEMMAGRSP
460 470 480 490 500
FDIITDNPDM NTEDYLFQVI LEKPIRIPRF LSVKASHVLK GFLNKDPKER
510 520 530 540 550
LGCRPQTGFS DIKSHAFFRS IDWDLLEKKQ TLPPFQPQIT DDYGLDNFDT
560 570 580 590
QFTSEPVQLT PDDEDVIKRI DQSEFEGFEY INPLLLSAEE SV
Length:592
Mass (Da):67,682
Last modified:July 27, 2011 - v2
Checksum:i690AD891C25BC311
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti197 – 1971D → G in AAA39983. (PubMed:1487145)Curated

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
M94632 mRNA. Translation: AAA39983.1.
AL670413, AL670227 Genomic DNA. Translation: CAM20048.1.
AL670227, AL670413 Genomic DNA. Translation: CAM20648.1.
CH466594 Genomic DNA. Translation: EDL15000.1.
CCDSiCCDS19026.1.
PIRiJC1480.
RefSeqiNP_032886.2. NM_008860.3.
UniGeneiMm.28561.

Genome annotation databases

EnsembliENSMUST00000030922; ENSMUSP00000030922; ENSMUSG00000029053.
GeneIDi18762.
KEGGimmu:18762.
UCSCiuc008wdc.1. mouse.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
M94632 mRNA. Translation: AAA39983.1 .
AL670413 , AL670227 Genomic DNA. Translation: CAM20048.1 .
AL670227 , AL670413 Genomic DNA. Translation: CAM20648.1 .
CH466594 Genomic DNA. Translation: EDL15000.1 .
CCDSi CCDS19026.1.
PIRi JC1480.
RefSeqi NP_032886.2. NM_008860.3.
UniGenei Mm.28561.

3D structure databases

ProteinModelPortali Q02956.
SMRi Q02956. Positions 13-182, 184-584.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

BioGridi 202203. 10 interactions.
IntActi Q02956. 3 interactions.
MINTi MINT-98101.

PTM databases

PhosphoSitei Q02956.

Proteomic databases

MaxQBi Q02956.
PaxDbi Q02956.
PRIDEi Q02956.

Protocols and materials databases

Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENSMUST00000030922 ; ENSMUSP00000030922 ; ENSMUSG00000029053 .
GeneIDi 18762.
KEGGi mmu:18762.
UCSCi uc008wdc.1. mouse.

Organism-specific databases

CTDi 5590.
MGIi MGI:97602. Prkcz.

Phylogenomic databases

eggNOGi COG0515.
GeneTreei ENSGT00760000118891.
HOGENOMi HOG000233033.
HOVERGENi HBG108317.
InParanoidi Q02956.
KOi K06069.
OMAi RCHVLVP.
OrthoDBi EOG7HF1J3.
TreeFami TF102004.

Enzyme and pathway databases

BRENDAi 2.7.11.13. 3474.
Reactomei REACT_196549. TGF-beta receptor signaling in EMT (epithelial to mesenchymal transition).
REACT_220092. GPVI-mediated activation cascade.

Miscellaneous databases

NextBioi 294953.
PROi Q02956.
SOURCEi Search...

Gene expression databases

Bgeei Q02956.
CleanExi MM_PRKCZ.
ExpressionAtlasi Q02956. baseline and differential.
Genevestigatori Q02956.

Family and domain databases

InterProi IPR000961. AGC-kinase_C.
IPR020454. DAG/PE-bd.
IPR011009. Kinase-like_dom.
IPR000270. OPR_PB1.
IPR002219. PE/DAG-bd.
IPR012233. PKC_zeta.
IPR017892. Pkinase_C.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR002290. Ser/Thr_dual-sp_kinase.
IPR008271. Ser/Thr_kinase_AS.
[Graphical view ]
PANTHERi PTHR24357:SF60. PTHR24357:SF60. 1 hit.
Pfami PF00130. C1_1. 1 hit.
PF00564. PB1. 1 hit.
PF00069. Pkinase. 1 hit.
PF00433. Pkinase_C. 1 hit.
[Graphical view ]
PIRSFi PIRSF000554. PKC_zeta. 1 hit.
PRINTSi PR00008. DAGPEDOMAIN.
SMARTi SM00109. C1. 1 hit.
SM00666. PB1. 1 hit.
SM00133. S_TK_X. 1 hit.
SM00220. S_TKc. 1 hit.
[Graphical view ]
SUPFAMi SSF56112. SSF56112. 1 hit.
PROSITEi PS51285. AGC_KINASE_CTER. 1 hit.
PS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
PS00479. ZF_DAG_PE_1. 1 hit.
PS50081. ZF_DAG_PE_2. 1 hit.
[Graphical view ]
ProtoNeti Search...

Publicationsi

« Hide 'large scale' publications
  1. "The cDNA sequence, expression pattern and protein characteristics of mouse protein kinase C-zeta."
    Goodnight J., Kazanietz M.G., Blumberg P.M., Mushinski F.J., Mischak H.
    Gene 122:305-311(1992) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA].
  2. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    Strain: C57BL/6J.
  3. Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C.
    Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
  4. "The cell-polarity protein Par6 links Par3 and atypical protein kinase C to Cdc42."
    Joberty G., Petersen C., Gao L., Macara I.G.
    Nat. Cell Biol. 2:531-539(2000) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH PARD6B.
    Tissue: Embryo.
  5. Cited for: FUNCTION IN INFLAMMATORY RESPONSE.
  6. "Lysine methylation of the NF-kappaB subunit RelA by SETD6 couples activity of the histone methyltransferase GLP at chromatin to tonic repression of NF-kappaB signaling."
    Levy D., Kuo A.J., Chang Y., Schaefer U., Kitson C., Cheung P., Espejo A., Zee B.M., Liu C.L., Tangsombatvisit S., Tennen R.I., Kuo A.Y., Tanjing S., Cheung R., Chua K.F., Utz P.J., Shi X., Prinjha R.K.
    , Lee K., Garcia B.A., Bedford M.T., Tarakhovsky A., Cheng X., Gozani O.
    Nat. Immunol. 12:29-36(2011) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION.

Entry informationi

Entry nameiKPCZ_MOUSE
AccessioniPrimary (citable) accession number: Q02956
Secondary accession number(s): A2AD76
Entry historyi
Integrated into UniProtKB/Swiss-Prot: July 1, 1993
Last sequence update: July 27, 2011
Last modified: October 29, 2014
This is version 155 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. Human and mouse protein kinases
    Human and mouse protein kinases: classification and index
  3. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3